Background: Shugoshin-1 (SGOL1) is a mammalian ortholog of Shugoshin in yeast and is essential for precise chromosome segregation during mitosis and meiosis. Aberrant SGOL1 expression was reported to be closely correlated with the malignant progression of various tumors. However, the expression pattern and biological function of SGOL1 in clear cell renal cell carcinoma (ccRCC) are unclear.
Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases provide mRNA expression data and outcome information for ccRCC patients. Immunohistochemistry (IHC) of ccRCC tissue chips verified SGOL1 protein expression in ccRCC patients. Data processing and visualization were performed with the UALCAN, TISIDB, TIMER, GSCA, LinkedOmics, and starBase databases. Gene Ontology (GO) annotation and gene set enrichment analysis (GSEA) were used to identify SGOL1-related biological functions and signaling pathways. Immune infiltration analysis was performed using the TISIDB database, ssGSEA algorithm, and TCGA-KIRC cohort. The biological role of SGOL1 in ccRCC was investigated using a series of in vitro cytological assays, including the MTT assay, EdU staining assay, flow cytometry analysis, Transwell assay, and wound healing assay.
Results: SGOL1 was highly expressed in ccRCC and linked to adverse clinicopathological parameters and unfavorable prognosis. Multivariate logistic regression and nomogram calibration suggested that SGOL1 might serve as an independent and reliable prognostic predictor of ccRCC. Functional enrichment analysis indicated that SGOL1 may be involved in the cell cycle, the p53 pathway, DNA replication, and T-cell activation. Furthermore, tumor microenvironment (TME) analysis suggested that SGOL1 was positively associated with Treg infiltration and immune checkpoint upregulation. In addition, we identified a potential SNHG17/PVT1/ZMIZ1-AS1-miR-23b-3p-SGOL1 axis correlated with ccRCC carcinogenesis and progression. Finally, we demonstrated that SGOL1 promoted ccRCC cell proliferation, migratory capacity, and invasion in vitro.
Conclusions: SGOL1 potentially functions as an oncogene in ccRCC progression and might contribute to the immunosuppressive TME by increasing Treg infiltration and checkpoint expression, suggesting that targeting SGOL1 could be a novel therapeutic strategy for the treatment of ccRCC patients.
Keywords: Immune infiltration; Malignant progression; Prognostic biomarkers; SGOL1; ccRCC.
© 2024. The Author(s).